title: Deficiency of phospholipase A2 receptor exacerbates ovalbumin-induced lung inflammation.
abstract: Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R(-/-)) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R(+/+)) mice, PLA2R(-/-) mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R(-/-) mice, intratracheally instilled [(125)I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R(+/+) mice. The degradation of the instilled [(125)I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R(-/-) mice than in PLA2R(+/+) mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.
authors.affiliation: Department of Internal Medicine II, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Tamaru
authors.forename: Hideto
authors.initials: H
authors.lastname: Mishina
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Soichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Jun-Ei
authors.initials: JE
authors.lastname: Obata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yokota
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Kohji
authors.initials: K
authors.lastname: Hanasaki
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kugiyama
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015777:Eicosanoids / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology; D005260:Female; D054500:Group IB Phospholipases A2 / Q000276:immunology / Q000378:metabolism*; D054509:Group X Phospholipases A2 / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology*; D054507:Receptors, Phospholipase A2 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015777:Eicosanoids; D054507:Receptors, Phospholipase A2; D010047:Ovalbumin; D054500:Group IB Phospholipases A2; D054509:Group X Phospholipases A2; C516366:Pla2g10 protein, mouse; C516203:Pla2g1b protein, mouse